We propose to study the soluble mediators involved in several states of immunologic unresponsiveness. Specifically, we are concerned with the nature of the soluble factor that mediates plasmacytoma-induced immunosuppression. We are also studying whether soluble immunosuppressive substances are active mediators in vivo in cases of antigen-specific immune unresponsiveness (i.e., states of immune tolerance) and in cases of antigen-nonspecific immune unresponsiveness (i.e., the phenomonon of antigenic competition). The existence of immunosuppressive soluble factors active in vivo will be studied by determining if the immune responsiveness of normal spleen cells is altered when placed in Millipore diffusion chambers. Inside tolerant mice or mice in which antigenic composition is elicited. If soluble immunosuppressive factors are demonstrated by this technique (as they have been in mice bearing plasmacytomas) then we will attempt to isolate and characterize those factors from serum or tissue extracts.